The purpose of the present guidelines on the radioiodine therapy (RAIT) of differentiated thyroid cancer (DTC) formulated by the European Association of Nuclear Medicine (EANM) Therapy Committee is to provide advice to nuclear medicine clinicians and other members of the DTC-treating community on how to ablate thyroid remnant or treat inoperable advanced DTC or both employing large 131-iodine (131I) activities. For this purpose, recommendations have been formulated based on recent literature and expert opinion regarding the rationale, indications and contraindications for these procedures, as well as the radioiodine activities and the administration and patient preparation techniques to be used. Recommendations also are provided on pre-RAIT history and examinations, patient counselling and precautions that should be associated with 131I iodine ablation and treatment. Furthermore, potential side effects of radioiodine therapy and alternate or additional treatments to this modality are reviewed. Appendices furnish information on dosimetry and post-therapy scintigraphy.

http://www.isotopterapi.se/Rekom/gl_radio_ther_259_883.pdf

Guidelines for radioiodine therapy of differentiated thyroid cancer

Radioiodine ((131)I) therapy of benign thyroid diseases was introduced 70 yr ago, and the patients treated since then are probably numbered in the millions. Fifty to 90% of hyperthyroid patients are cured within 1 yr after (131)I therapy. With longer follow-up, permanent hypothyroidism seems inevitable in Graves' disease, whereas this risk is much lower when treating toxic nodular goiter. The side effect causing most concern is the potential induction of ophthalmopathy in predisposed individuals. The response to (131)I therapy is to some extent related to the radiation dose. However, calculation of an exact thyroid dose is error-prone due to imprecise measurement of the (131)I biokinetics, and the importance of internal dosimetric factors, such as the thyroid follicle size, is probably underestimated. Besides these obstacles, several potential confounders interfere with the efficacy of (131)I therapy, and they may even interact mutually and counteract each other. Numerous studies have evaluated the effect of (131)I therapy, but results have been conflicting due to differences in design, sample size, patient selection, and dose calculation. It seems clear that no single factor reliably predicts the outcome from (131)I therapy. The individual radiosensitivity, still poorly defined and impossible to quantify, may be a major determinant of the outcome from (131)I therapy. Above all, the impact of (131)I therapy relies on the iodine-concentrating ability of the thyroid gland. The thyroid (131)I uptake (or retention) can be stimulated in several ways, including dietary iodine restriction and use of lithium. In particular, recombinant human thyrotropin has gained interest because this compound significantly amplifies the effect of (131)I therapy in patients with nontoxic nodular goiter.

Radioiodine Therapy in Benign Thyroid Diseases: Effects, Side Effects, and Factors Affecting Therapeutic Outcome

Background: Thyroid remnant ablation of differentiated thyroid carcinoma (DTC) patients is traditionally performed after levothyroxine withdrawal. Recombinant human TSH (rhTSH) administration increases serum TSH levels without inducing hypothyroidism. Aim: The aim of the study was to investigate the frequency of chromosome translocations in DTC patients after the first 131I therapeutic dose and compare the frequency of translocations between DTC patients off levothyroxine and those receiving rhTSH. Patients and Methods: A total of 20 DTC patients were randomly assigned to levothyroxine withdrawal [(30 d) group A; n=10, nine women; mean age 48.5± 19.2 yr] or rhTSH injections [(0.9 mg im per 2 consecutive days) group B; n=10, eight women; mean age 50.4± 18.8 yr] before undergoing 131I activity (3.7 GBq). The frequency of translocations in peripheral lymphocytes was analyzed by tricolor fluorescence in situ hybridization with whole-chromosome-specific probes for chromosomes 1, 4, and 8. Lymphocytes were stai...

Chromosome translocation frequency after radioiodine thyroid remnant ablation: a comparison between recombinant human thyrotropin stimulation and prolonged levothyroxine withdrawal.

Background
For patients with differentiated thyroid cancer (DTC) following thyroidectomy, thyroid hormone withdrawal (THW) for four to six weeks has been used for decades to increase serum thyroid-stimulating hormone (TSH) concentrations in order to enhance iodine-131 uptake by normal thyroid cells and differentiated thyroid tumour cells. Exogenous stimulation with recombinant human thyroid-stimulating hormone (rhTSH) offers an alternative to THW while avoiding the morbidity of hypothyroidism. However, the efficacy of rhTSH-aided iodine-131 treatment for residual or metastatic DTC has not been prospectively assessed.

Objectives
To assess the effects of rhTSH-aided radioiodine treatment for normal residual or metastatic DTC.

Search methods
We obtained studies from computerised searches of MEDLINE, EMBASE and The Cochrane Library (all until November 2009), and paper collections of conferences held in Chinese.

Selection criteria
Randomised controlled clinical trials and quasi-randomised controlled clinical trials comparing the effects of rhTSH with THW on iodine-131 treatment for residual or metastatic differentiated thyroid cancer with at least six months of follow up.

Data collection and analysis
Two authors independently assessed risk of bias and extracted data.

Main results
Altogether 223 patients with DTC participated in four trials. Overall, studies had a high risk of bias. We found no statistically significant differences between rhTSH and THW treatment in terms of successful ablation rate but significant benefits in radiation exposure to blood and bone marrow. One trial reported on benefits in some domains of health-related quality of life. There were no deaths and no serious adverse effects in DTC patients treated with either rhTSH or THW. Maximum follow up was 12 months. None of the included trials investigated complete or partial remission of metastatic tumour, secondary malignancies or economic outcomes. We did not find sufficient data comparing rhTSH with THW-aided radioiodine treatment for metastatic DTC.

Authors' conclusions
Results from four randomised controlled clinical trials suggest that rhTSH is as effective as THW on iodine-131 thyroid remnant ablation, with limited data on significant benefits in decreased whole body radiation exposure and health-related quality of life. It is still uncertain whether lower iodine-131 doses (1110 MBq or 1850 MBq versus 3700 MBq) are equally effective for remnant ablation under rhTSH stimulation. Randomised controlled clinical trials are needed to guide treatment selection for metastatic differentiated thyroid cancer.

/pdf/recombinant-human-thyrotropin-rhtsh-aided-radioiodine-cl544pp5m2.pdf

Recombinant human thyrotropin (rhTSH) aided radioiodine treatment for residual or metastatic differentiated thyroid cancer.

AIM Recombinant human thyroid-stimulating hormone (rhTSH) recently was approved as an alternative to thyroid hormone withholding (THW) to elevate TSH for thyroid remnant ablation in differentiated thyroid carcinoma patients. High ablation success rates are reported with diverse rhTSH-aided (131)I activities. Improved renal function causes approximately 50% faster radioiodine clearance under euthyroidism versus hypothyroidism. Knowledge of comparative remnant radioiodine kinetics, particularly the remnant radiation dose in Gy/GBq of administered (131)I activity (RDpA), could assist in choosing rhTSH-aided ablative activities. MATERIAL AND METHODS To compare the RDpA, determined through (124)I-positron emission tomography/computed tomography (PET/CT), under the two stimulation methods, we retrospectively divided into two groups 55 consecutive totally-thyroidectomized, radioiodine-naive patients. The rhTSH group (n=16) received (124)I on thyroid hormone, 24 h after two consecutive daily intramuscular injections of rhTSH, 0.9 mg. The THW group (n=39) received (124)I after weeks-long THW, when serum TSH first measured > or = 25 mIU/L. We performed PET investigations 4 h, 24 h, 48 h, 72 h and 96 h and PET/CT 25 h after (124)I administration. RESULTS Median stimulated serum thyroglobulin was 15 times higher (p=0.023) and M1 disease almost twice as prevalent (p=0.05) in rhTSH versus THW patients. Mean+/-standard deviation RDpA was statistically equivalent between the groups: rhTSH, 461+/-600 Gy/GBq, THW, 302+/-329 Gy/GBq, two-sided p=0.258. CONCLUSIONS rhTSH or THW deliver statistically equivalent radiation doses to thyroid remnant and may be chosen based on safety, quality-of-life, convenience and pharmacoeconomic factors. Institutional fixed radioiodine activities formulated for use with THW need not be adjusted for rhTSH-aided ablation.

Thyroid remnant dose: 124I-PET/CT dosimetric comparison of rhTSH versus thyroid hormone withholding before radioiodine remnant ablation in differentiated thyroid cancer.

Comparison between remnant and red marrow adsorbed dose in thyroid cancer patients submitted to 131I ablative therapy after r-TSH stimulation versus hypothyroidism induced by L-thyroxine withdrawl

A simple model to predict the final mass of Graves’ disease thyroids submitted to 131I therapy

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Comparison between remnant and red marrow adsorbed dose in thyroid cancer patients submitted to 131I ablative therapy after r-TSH stimulation versus hypothyroidism induced by L-thyroxine withdrawl

A simple model to predict the final mass of Graves’ disease thyroids submitted to 131I therapy